Dose-dependent effects of capsaicin nasal challenge: In vivo evidence of human airway neurogenic inflammation

Background: Nerve involvement has been implicated in the pathophysiology of chronic respiratory inflammatory diseases. Peptidergic nerve stimulation has been shown to induce leukocyte activation and plasma extravasation in the airways of various animal species. The occurrence of this phenomenon of neurogenic inflammation in the human airway, however, has not been established. Objective: We conducted this study to determine whether neuronal stimulation can induce reproducible and dose-dependent inflammatory changes in the human upper airway. Methods: Ten volunteers with active allergic rhinitis participated in the study. Capsaicin, the pungent component of hot pepper that specifically stimulates afferent nerve fibers, was administered by means of nasal spray in doses of 1 mu g, 10 mu g, and 100 mu g in a double-blind, randomized, crossover manner with 1 week between doses. Symptom scores before and after capsaicin nasal challenge were recorded by using visual analog scales. Nasal lavage fluids collected before and at 30 minutes, 1 hour, and 4 hours after capsaicin challenge were analyzed for leukocyte counts; albumin and lysozyme levels were measured to evaluate effects on plasma leakage and gland secretion, respectively. Results: Capsaicin nasal challenge produced symptoms of burning, congestion, and rhinorrhea. Leukocyte counts or albumin and lysozyme levels were not significantly increased after administration of 1 mu g of capsaicin at any time point. On the other hand, there were significant increases in leukocyte counts 1 hour (p < 0.05) and 4 hours (p = 0.008) after 10 mu g of capsaicin and 30 minutes (p = 0.009), 1 hour (p = 0.007), and 4 hours (p = 0.007) after 100 mu g of capsaicin. Albumin and lysozyme levels were both significantly in creased 30 minutes after 10 mu g and 100 mu g of capsaicin (p = 0.005 for both). Comparison of changes in symptom scores, leukocyte counts, and albumin and lysozyme levels among the three capsaicin challenges indicated generally increasing effects with higher capsaicin doses. Conclusion: Capsaicin-sensitive nerve stimulation in subjects with active allergic rhinitis produces reproducible and dose-dependent leukocyte influx, albumin leakage, and glandular secretion. These results provide in vivo evidence for the occurrence of neurogenic inflammation in the human upper airway with active allergic disease.